The pore domain in glutamate-gated ion channels: Structure, drug binding and similarity with potassium channels

Ionotropic glutamate receptors in the CNS excitatory synapses of vertebrates are involved in numerous physiological and pathological processes. Decades of intensive studies greatly advanced our understanding of molecular organization of these transmembrane proteins. Here we focus on the channel pore domain, its selectivity filter and the activation gate, and the pore block by organic ligands. We compare findings from indirect experimental approaches, including site-directed mutagenesis, with recent crystal and cryo-EM structures of different channels in different functional states and complexed with different ligands. We summarize remaining uncertainties and unresolved problems related to the channel structure, function and pharmacology.